Pharmacokinetics of progesterone in lactating dairy cows: Gaining some insights into the metabolism from kinetic modeling
- Autores
- Turino, Ludmila Noelia; Mariano, Rodolfo Nicolás; Cabrera, Maria Ines; Scándolo, Daniel E.; Maciel, Martín G.; Grau, Ricardo José Antonio
- Año de publicación
- 2010
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Progesterone pharmacokinetics were analyzed for plasma hormone concentrations ranging from linear to saturated metabolism in lactating Holstein cows with differing daily milk yields. The adequacy of 2-coupled first-order (bi-exponential equation), hyperbolic (Michaelis-Menten equation), and sigmoidal (Hill equation) kinetic models to describe the experimental progesterone pharmacokinetic profiles was examined on a statistical basis. After nonlinear regression andstatistical analysis of the data-fitting capability, a simple one-compartment model based on Hill equation proved to be most adequate. This model indicates an enzyme-catalyzed metabolism of progesterone involving cooperative substrate-binding sites, resulting from allosteric effects that yield a sigmoidal saturation rate curve. Kinetic parameters were estimated for 2 groups of lactating Holstein cows with different daily milk yields. We found, for the first time, a remarkable quantitative agreement of the Hill coefficient value with that reported in pharmacokinetic studies involving cytochrome P450, family 3, subfamily A (CYP3A)-mediated reactions in other mammals, humans included. It seems that positive cooperativity makes enzymes much more sensitive to plasma progesterone concentration, and their activities can undergo significant changes in a narrow range of concentration as characteristic of sigmoidal behavior. Therefore, the values of classical pharmacokinetic parameters, such as the elimination constant, half-life, and clearance rate, were found to be highly dependent on the plasma progesterone concentration.
Fil: Turino, Ludmila Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina
Fil: Mariano, Rodolfo Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina
Fil: Cabrera, Maria Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina
Fil: Scándolo, Daniel E.. Instituto Nacional de Tecnologia Agropecuaria. Centro Regional Santa Fe. Estacion Experimental Agropecuaria Rafaela. Agencia de Extension Rural Rafaela; Argentina
Fil: Maciel, Martín G.. Instituto Nacional de Tecnologia Agropecuaria. Centro Regional Santa Fe. Estacion Experimental Agropecuaria Rafaela. Agencia de Extension Rural Rafaela; Argentina
Fil: Grau, Ricardo José Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina - Materia
-
Progesterone
Pharmacokinetics
Dairy Cows - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/246262
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Pharmacokinetics of progesterone in lactating dairy cows: Gaining some insights into the metabolism from kinetic modelingTurino, Ludmila NoeliaMariano, Rodolfo NicolásCabrera, Maria InesScándolo, Daniel E.Maciel, Martín G.Grau, Ricardo José AntonioProgesteronePharmacokineticsDairy Cowshttps://purl.org/becyt/ford/4.2https://purl.org/becyt/ford/4Progesterone pharmacokinetics were analyzed for plasma hormone concentrations ranging from linear to saturated metabolism in lactating Holstein cows with differing daily milk yields. The adequacy of 2-coupled first-order (bi-exponential equation), hyperbolic (Michaelis-Menten equation), and sigmoidal (Hill equation) kinetic models to describe the experimental progesterone pharmacokinetic profiles was examined on a statistical basis. After nonlinear regression andstatistical analysis of the data-fitting capability, a simple one-compartment model based on Hill equation proved to be most adequate. This model indicates an enzyme-catalyzed metabolism of progesterone involving cooperative substrate-binding sites, resulting from allosteric effects that yield a sigmoidal saturation rate curve. Kinetic parameters were estimated for 2 groups of lactating Holstein cows with different daily milk yields. We found, for the first time, a remarkable quantitative agreement of the Hill coefficient value with that reported in pharmacokinetic studies involving cytochrome P450, family 3, subfamily A (CYP3A)-mediated reactions in other mammals, humans included. It seems that positive cooperativity makes enzymes much more sensitive to plasma progesterone concentration, and their activities can undergo significant changes in a narrow range of concentration as characteristic of sigmoidal behavior. Therefore, the values of classical pharmacokinetic parameters, such as the elimination constant, half-life, and clearance rate, were found to be highly dependent on the plasma progesterone concentration.Fil: Turino, Ludmila Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Mariano, Rodolfo Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Cabrera, Maria Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Scándolo, Daniel E.. Instituto Nacional de Tecnologia Agropecuaria. Centro Regional Santa Fe. Estacion Experimental Agropecuaria Rafaela. Agencia de Extension Rural Rafaela; ArgentinaFil: Maciel, Martín G.. Instituto Nacional de Tecnologia Agropecuaria. Centro Regional Santa Fe. Estacion Experimental Agropecuaria Rafaela. Agencia de Extension Rural Rafaela; ArgentinaFil: Grau, Ricardo José Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaAmerican Dairy Science Association2010-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/246262Turino, Ludmila Noelia; Mariano, Rodolfo Nicolás; Cabrera, Maria Ines; Scándolo, Daniel E.; Maciel, Martín G.; et al.; Pharmacokinetics of progesterone in lactating dairy cows: Gaining some insights into the metabolism from kinetic modeling; American Dairy Science Association; Journal of Dairy Science; 93; 3; 1-2010; 988-9990022-0302CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3168/jds.2009-2519info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0022030210000664info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:56:18Zoai:ri.conicet.gov.ar:11336/246262instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:56:19.127CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Pharmacokinetics of progesterone in lactating dairy cows: Gaining some insights into the metabolism from kinetic modeling |
title |
Pharmacokinetics of progesterone in lactating dairy cows: Gaining some insights into the metabolism from kinetic modeling |
spellingShingle |
Pharmacokinetics of progesterone in lactating dairy cows: Gaining some insights into the metabolism from kinetic modeling Turino, Ludmila Noelia Progesterone Pharmacokinetics Dairy Cows |
title_short |
Pharmacokinetics of progesterone in lactating dairy cows: Gaining some insights into the metabolism from kinetic modeling |
title_full |
Pharmacokinetics of progesterone in lactating dairy cows: Gaining some insights into the metabolism from kinetic modeling |
title_fullStr |
Pharmacokinetics of progesterone in lactating dairy cows: Gaining some insights into the metabolism from kinetic modeling |
title_full_unstemmed |
Pharmacokinetics of progesterone in lactating dairy cows: Gaining some insights into the metabolism from kinetic modeling |
title_sort |
Pharmacokinetics of progesterone in lactating dairy cows: Gaining some insights into the metabolism from kinetic modeling |
dc.creator.none.fl_str_mv |
Turino, Ludmila Noelia Mariano, Rodolfo Nicolás Cabrera, Maria Ines Scándolo, Daniel E. Maciel, Martín G. Grau, Ricardo José Antonio |
author |
Turino, Ludmila Noelia |
author_facet |
Turino, Ludmila Noelia Mariano, Rodolfo Nicolás Cabrera, Maria Ines Scándolo, Daniel E. Maciel, Martín G. Grau, Ricardo José Antonio |
author_role |
author |
author2 |
Mariano, Rodolfo Nicolás Cabrera, Maria Ines Scándolo, Daniel E. Maciel, Martín G. Grau, Ricardo José Antonio |
author2_role |
author author author author author |
dc.subject.none.fl_str_mv |
Progesterone Pharmacokinetics Dairy Cows |
topic |
Progesterone Pharmacokinetics Dairy Cows |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/4.2 https://purl.org/becyt/ford/4 |
dc.description.none.fl_txt_mv |
Progesterone pharmacokinetics were analyzed for plasma hormone concentrations ranging from linear to saturated metabolism in lactating Holstein cows with differing daily milk yields. The adequacy of 2-coupled first-order (bi-exponential equation), hyperbolic (Michaelis-Menten equation), and sigmoidal (Hill equation) kinetic models to describe the experimental progesterone pharmacokinetic profiles was examined on a statistical basis. After nonlinear regression andstatistical analysis of the data-fitting capability, a simple one-compartment model based on Hill equation proved to be most adequate. This model indicates an enzyme-catalyzed metabolism of progesterone involving cooperative substrate-binding sites, resulting from allosteric effects that yield a sigmoidal saturation rate curve. Kinetic parameters were estimated for 2 groups of lactating Holstein cows with different daily milk yields. We found, for the first time, a remarkable quantitative agreement of the Hill coefficient value with that reported in pharmacokinetic studies involving cytochrome P450, family 3, subfamily A (CYP3A)-mediated reactions in other mammals, humans included. It seems that positive cooperativity makes enzymes much more sensitive to plasma progesterone concentration, and their activities can undergo significant changes in a narrow range of concentration as characteristic of sigmoidal behavior. Therefore, the values of classical pharmacokinetic parameters, such as the elimination constant, half-life, and clearance rate, were found to be highly dependent on the plasma progesterone concentration. Fil: Turino, Ludmila Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina Fil: Mariano, Rodolfo Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina Fil: Cabrera, Maria Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina Fil: Scándolo, Daniel E.. Instituto Nacional de Tecnologia Agropecuaria. Centro Regional Santa Fe. Estacion Experimental Agropecuaria Rafaela. Agencia de Extension Rural Rafaela; Argentina Fil: Maciel, Martín G.. Instituto Nacional de Tecnologia Agropecuaria. Centro Regional Santa Fe. Estacion Experimental Agropecuaria Rafaela. Agencia de Extension Rural Rafaela; Argentina Fil: Grau, Ricardo José Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina |
description |
Progesterone pharmacokinetics were analyzed for plasma hormone concentrations ranging from linear to saturated metabolism in lactating Holstein cows with differing daily milk yields. The adequacy of 2-coupled first-order (bi-exponential equation), hyperbolic (Michaelis-Menten equation), and sigmoidal (Hill equation) kinetic models to describe the experimental progesterone pharmacokinetic profiles was examined on a statistical basis. After nonlinear regression andstatistical analysis of the data-fitting capability, a simple one-compartment model based on Hill equation proved to be most adequate. This model indicates an enzyme-catalyzed metabolism of progesterone involving cooperative substrate-binding sites, resulting from allosteric effects that yield a sigmoidal saturation rate curve. Kinetic parameters were estimated for 2 groups of lactating Holstein cows with different daily milk yields. We found, for the first time, a remarkable quantitative agreement of the Hill coefficient value with that reported in pharmacokinetic studies involving cytochrome P450, family 3, subfamily A (CYP3A)-mediated reactions in other mammals, humans included. It seems that positive cooperativity makes enzymes much more sensitive to plasma progesterone concentration, and their activities can undergo significant changes in a narrow range of concentration as characteristic of sigmoidal behavior. Therefore, the values of classical pharmacokinetic parameters, such as the elimination constant, half-life, and clearance rate, were found to be highly dependent on the plasma progesterone concentration. |
publishDate |
2010 |
dc.date.none.fl_str_mv |
2010-01 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/246262 Turino, Ludmila Noelia; Mariano, Rodolfo Nicolás; Cabrera, Maria Ines; Scándolo, Daniel E.; Maciel, Martín G.; et al.; Pharmacokinetics of progesterone in lactating dairy cows: Gaining some insights into the metabolism from kinetic modeling; American Dairy Science Association; Journal of Dairy Science; 93; 3; 1-2010; 988-999 0022-0302 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/246262 |
identifier_str_mv |
Turino, Ludmila Noelia; Mariano, Rodolfo Nicolás; Cabrera, Maria Ines; Scándolo, Daniel E.; Maciel, Martín G.; et al.; Pharmacokinetics of progesterone in lactating dairy cows: Gaining some insights into the metabolism from kinetic modeling; American Dairy Science Association; Journal of Dairy Science; 93; 3; 1-2010; 988-999 0022-0302 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/doi/10.3168/jds.2009-2519 info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0022030210000664 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf application/pdf application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
American Dairy Science Association |
publisher.none.fl_str_mv |
American Dairy Science Association |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
reponame_str |
CONICET Digital (CONICET) |
collection |
CONICET Digital (CONICET) |
instname_str |
Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.name.fl_str_mv |
CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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1842269397910028288 |
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13.13397 |